Dr Roberta Mazzieri

Dr Roberta Mazzieri obtained her PhD in Genetic Science from the University of Pavia (Italy) and subsequently undertook one post-doctoral position at the New York University (USA) and two at the San Raffaele Scientific Institute in Milan (Italy). Since her PhD studies, she focused on understanding the tumor microenvironment by examining a number of related molecular pathways including the uPA/uPAR system and TGFß1 activation. During her last postdoc with Prof. Naldini, she made her most significant and clinically-applicable contribution to cancer research by exploiting advanced gene transfer technologies to study the interplay between tumour associated macrophages and tumor angiogenesis. She demonstrated that targeting the ANG2/TIE2 pathway inhibits tumor angiogenesis, growth, and metastasis by disabling the pro-angiogenic activity of tumour associated Tie2-expressing macrophages (TEMs), thus impeding the emergence of evasive resistance to anti-angiogenic therapy. In 2011 this work was featured as cover article in Cancer Cell. Moreover, by turning TEMs into efficient delivery vehicles, she worked to target a key immune modulatory protein, IFN-alpha, to tumors and achieved substantial antitumor activity in several tumor models including a human model of breast cancer. This work was recently published as cover article in Science Translational Medicine. In 2012 she was nominated by the Young Ambassadors from the Metastasis Research Society (MRS) to speak at MRS meeting in recognition of her potential to launch independent research and contribute to high-quality publications.

The same year she was recruited by the University of Queensland (Brisbane) to establish her own research group.

At the UQ-Diamantina Institute she is now continuing her work on targeting pro-tumoural macrophages to inhibit tumour progression with a specific focus on breast cancer metastasis. She is also continuing her work on demonstrating the therapeutic potential of turning tumour infiltrating macrophages into efficient delivery vehicles of anti-tumoural biomolecules.

Research projects

Targeting the proangiogenic and immunosuppressive tumour microenvironment in primary and metastatic breast cancer.

Despite many decades of basic and clinical research aimed at controlling tumour growth, cancer continues to be a deadly disease. Too often therapeutic failures result in evasive resistance, cancer recurrence and metastasis. New strategies are therefore highly needed. One area of cancer biology that shows promise in identifying new druggable targets is the tumour microenvironment. We are trying to modulate two important aspects of the tumour microenvironment: tumour angiogenesis and immunosuppression using a strategy by us previously described and that, we think, could be effectively combined with emerging cancer immunotherapies. We have identified and characterized a specific subpopulation of pro-tumoural macrophages: the TIE2-expressing monocytes/macrophages (TEMs) endowed with pro-angiogeic and immunosuppressive activities. More recently, we have demonstrated for the first time that targeting the ANG2/TIE2 pathway inhibits tumour angiogenesis, growth, and metastasis. In addition, blocking ANG2/TIE2 disables the pro angiogenic activity of TEMs and impedes the emergence of evasive resistance to anti-angiogenic therapy. ANG2 also modulates the immunosuppressive activity of TEMs. The establishment of an immunosuppressive tumour microenvironment is one of the fundamental hallmarks of cancer and the major impediment to the successful application of anti-tumour immunotherapy. With the final goal of developing new and more effective antitumour and anti-metastasis therapies, we are investigating whether the blockade of ANG2 results in a less permissive and less immunosuppressive tumour microenvironment able to enhance the efficacy of established cancer immunotherapies.

Breast cancer is the second leading cause of cancer-related death in women in Australia. Although therapeutic approaches, such as surgery, chemotherapy, radiation or endocrine therapy, have reduced cancer specific mortality, there still are many therapeutic failures, which result in cancer recurrence, metastasis and death. One area of breast cancer biology that shows promise in identifying new therapeutic targets is the tumour microenvironment. By fostering tumour growth and progression, supporting angiogenesis and tissue remodelling, and by counteracting host immunity, the tumour microenvironment plays an important role in modulating the tumour response to therapies. In particular, the establishment of an immunosuppressive tumour microenvironment is one of the hallmarks of cancer and the major impediment to the successful application of cancer immunotherapy. As a strategy aimed at reverting the immunosuppressive microenvironment, we turned a pro-tumoural population of macrophages, the TIE2 expressing monocyte/macrophages, into cellular vehicles for the tumour targeted delivery of IFN-alpha. This was achieved by exploiting their tumour homing capability and selective expression of the angiopoietin TIE2 receptor, two important characteristics of TEMs by us previously described. This cell- and gene-based delivery therapy strongly inhibited primary breast cancer tumours and breast cancer lung metastasis in mouse and human hematochimeric models. Importantly, the multiple activities of type I IFNs in the complex network of cell interactions that lead to activation and deployment of immune responses may also represent a valid strategy to promote and improve the outcome of cancer immunotherapy and this is what we are investigating in this project.

Researcher biography

Dr Roberta Mazzieri obtained her PhD in Genetic Science from the University of Pavia (Italy) and subsequently undertook one post-doctoral position at the New York University (USA) and two at the San Raffaele Scientific Institute in Milan (Italy). Since her PhD studies, she focused on understanding the tumor microenvironment by examining a number of related molecular pathways including the uPA/uPAR system and TGFß1 activation. During her last postdoc with Prof. Naldini, she made her most significant and clinically-applicable contribution to cancer research by exploiting advanced gene transfer technologies to study the interplay between tumour associated macrophages and tumor angiogenesis. She demonstrated that targeting the ANG2/TIE2 pathway inhibits tumor angiogenesis, growth, and metastasis by disabling the pro-angiogenic activity of tumour associated Tie2-expressing macrophages (TEMs), thus impeding the emergence of evasive resistance to anti-angiogenic therapy. In 2011 this work was featured as cover article in Cancer Cell. Moreover, by turning TEMs into efficient delivery vehicles, she worked to target a key immune modulatory protein, IFN-alpha, to tumors and achieved substantial antitumor activity in several tumor models including a human model of breast cancer. This work was published as cover article in Science Translational Medicine.

In 2012 she was nominated by the Young Ambassadors from the Metastasis Research Society (MRS) to speak at MRS meeting in recognition of her potential to launch independent research and contribute to high-quality publications. The same year she was recruited by the University of Queensland (Brisbane, Australia) to establish her own research group. At the UQ-Diamantina Institute she is now continuing her work on targeting pro-tumoural macrophages to inhibit tumour progression with a specific focus on breast cancer metastasis. She is also continuing her work on demonstrating the therapeutic potential of turning tumour infiltrating macrophages into efficient delivery vehicles of anti-tumoural biomolecules. In particular, she is now exploring the potential of this strategy to improve the outcome of emerging immunotherapies in breast cancer and Glioblastoma. She is also collaborating in further understanding the role of myeloid cells in tumor progression.